Axin1 Conditional Knockout mouse models

Axin1, the mouse ortholog of human AXIN1, encodes the concentration limiting scaffold of the beta-catenin destruction complex, using an N-terminal RGS domain to dock APC, a central segment to bind GSK3 beta and CK1 alpha, and a C-terminal DIX domain to polymerize and to engage Dishevelled DIX domains at activated LRP6 signalosomes. Its abundance is set by tankyrase mediated PARsylation and RNF146 dependent degradation, which is exactly why tankyrase inhibitors raise AXIN1 levels and suppress Wnt output. Loss of function AXIN1 mutations occur in hepatocellular carcinoma and hepatoblastoma, producing ligand-independent signaling equivalent to APC truncation. Germline null causes embryonic lethality with axis duplication in the classic Fused mutant, so hepatocyte or intestinal conditional alleles are required for tumor work. Axin2 is transcriptionally induced by Wnt and partially compensates, so double conditional stocks reveal phenotypes single deletion hides. Choose nulls for dependency and tankyrase pharmacology, and stabilization-resistant knockins to interrogate degradation control.

Tissue restricted knockout of Axin1 keeps wild type function everywhere else. Breeding is often more robust, and the setup mirrors patient biology where mutations arise in a subset of cells.